Clinical, pathological, and radiological features in the diagnosis and prognosis of carcinoma ex pleomorphic adenoma: a series of systematic reviews

Abstract

Introduction: Carcinoma ex Pleomorphic Adenoma (CXPA) is a rare primary salivary gland malignancy, typically arising from a pre-existing pleomorphic adenoma (PA). The existing literature shows a broad range of survival outcomes, making it difficult to guide timing of surgery for its benign counterpart, PA.

Aims: This thesis examines clinical, radiological, and pathological features of CXPA which may affect survival outcomes and guide clinical management.

Methods: Series of three systematic reviews derived from peer-reviewed and grey literature. Full-text review, data extraction, and risk of bias assessment were conducted by two independent authors. Inclusion criteria were study-specific, but studies examined humans with histological diagnosis of major or minor salivary gland CXPA. All studies were registered prospectively on PROSPERO(CRD42021238544, CRD42022355626, CRD42023421449)

Results: Clinical outcomes were examined in 39 studies (n=5637). Median overall survival at one, five, and ten years were 90.0%, 61.9%, and 45.0%. Higher staging, T stage,nodal disease, grading, and invasion ≥1.5mm had worse outcomes. Histological subtype, perineural invasion, and radiotherapy did not show a consistent trend. Molecular factors were examined in 55 studies (n=1322). Examined biomarkers included p53, HER2, AR, EGFR, PLAG1, ERBB,ER/PR, and HMGA2. Predicted incidence was calculated with meta-analysis. Significant differences were shown compared to PA and salivary duct carcinoma. Pre-operative radiological features were examined in 12 studies(n=426). MRI with lower mean ADC values and heterogenous T2 intensity indicated CXPA. Risk of bias was high for molecular and radiology reviews.

Conclusions: CXPA is an evolving entity with clinical, radiological, and molecular features which can distinguish it from other malignant salivary gland tumours. Prospective multi-center collaborative studies should be conducted to further explore the therapeutic implications of this rare entity.